Polymer Conjugation of Docosahexaenoic Acid Potentiates Cardioprotective Therapy in Preclinical Models of Myocardial Ischemia/Reperfusion Injury.

While coronary angioplasty represents an effective treatment option following acute myocardial infarction, the reperfusion of the occluded coronary artery can prompt ischemia-reperfusion (I/R) injury that significantly impacts patient outcomes. As ω-3 polyunsaturated fatty acids (PUFAs) have proven, yet limited cardioprotective abilities, an optimized polymer-conjugation approach is reported that improves PUFAs bioavailability to enhance cardioprotection and recovery in animal models of I/R-induced injury. Poly-l-glutamic acid (PGA) conjugation improves the solubility and stability of di-docosahexaenoic acid (diDHA) under physiological conditions and protects rat neonatal ventricular myocytes from I/R injury by reducing apoptosis, attenuating autophagy, inhibiting reactive oxygen species generation, and restoring mitochondrial membrane potential. Enhanced protective abilities are associated with optimized diDHA loading and evidence is provided for the inherent cardioprotective potential of PGA itself. Pretreatment with PGA-diDHA before reperfusion in a small animal I/R model provides for cardioprotection and limits area at risk (AAR). Furthermore, the preliminary findings suggest that PGA-diDHA administration in a swine I/R model may provide cardioprotection, limit edema and decrease AAR. Overall, the evaluation of PGA-diDHA in relevant preclinical models provides evidence for the potential of polymer-conjugated PUFAs in the mitigation of I/R injury associated with coronary angioplasty.

Left ventricular myocardial dysfunction in arrhythmogenic cardiomyopathy with left ventricular involvement: A door to improving diagnosis.

BACKGROUND: Diagnostic Task Force Criteria (TFC) for arrhythmogenic cardiomyopathy (AC) exhibit poor performance for left dominant forms. TFC only include right ventricular (RV) dysfunction (akinesia, dyssynchrony, volumes and ejection fraction). Moreover, cardiac magnetic resonance imaging (CMRI) assessment of left ventricular (LV) dyssynchrony has hitherto not been described. Thus, we aimed to comprehensively characterize LV CMRI behavior in AC patients. METHODS: Thirty-five AC patients with LV involvement and twenty-three non-affected family members (controls) were enrolled. Feature-tracking analysis was applied to cine CMRI to assess LV ejection fraction (LVEF), LV end-systolic and end-diastolic volume indexes, strain values and dyssynchrony. Regions with more frequent strain and dyssynchrony impairment were also studied. RESULTS: Radial dyssynchrony and LVEF were selected (sensitivities 54.3% and 48.6%, respectively at 100% specificity), with a threshold of 70 ms for radial dyssynchrony and 48.5% for LVEF. 71.4% of patients exceeded these thresholds (31.4% both, 22.9% only dyssynchrony and 17.1% only LVEF). Considering these cut-off values as a novel combined criterion, 30% of patients with 'borderline' or 'possible' AC following 2010 TFC would move to a 'definite' AC diagnosis. Strain was globally impaired whereas dyssynchronous regions were more often apical and located at the inferolateral wall. CONCLUSIONS: Mirroring the RV evaluation, we suggest including LVEF and LV dyssynchrony to improve the diagnosis of AC. Two independent mechanisms can be claimed in AC patients with LV involvement: 1) decreased myocardial deformation with global LV affectation and 2) delayed myocardial contraction at localized regions.

Assessment of late cardiomyopathy by magnetic resonance imaging in patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and idarubicin.

Late cardiomyopathy CMP is regarded as a potential severe long-term complication after anthracycline-based regimens for acute promyelocitic leukaemia (APL). We assess by MRI the incidence and severity of clinical and subclinical long-term CMP in a cohort of adult APL patients in first complete remission with PETHEMA trials. Adult patients diagnosed with APL in first complete remission lasting ≥2 years underwent anamnesis and physical examination and were asked to perform a cardiac MRI. Clinical CMP was defined as radiographic and physical signs of heart failure accompanied by symptoms or by left ventricle ejection fraction (LVEF) <45% by MRI with or without symptoms. Subclinical CMP was defined as the following MRI abnormalities: LVEF 45-50% or late gadolinium enhancement or two or more of LVEF ≤55%, left ventricle end-diastolic volume index ≥98 ml/m2, left ventricle end-systolic volume index ≥38 ml/m2, right ventricle end-diastolic volume index ≥106 ml/m2 and regional wall motion abnormalities. Of the 82 patients enrolled in the study, median cumulative dose of anthracyclines (doxorubicin equivalence) was 650 mg/m2, and median time from APL diagnosis to the study was 87 months (range, 24-195). Seven out of 57 patients with available MRI (12%) had subclinical CMP (all of them showed late gadolinium enhancement in MRI), and none had clinical CMP. Among the 25 patients without MRI, none had CMP by chest X-ray and physical assessment. In summary, we found 12% of subclinical and no clinical late CMP assessed by MRI in APL patients treated with PETHEMA protocols. Due to the low number of patients, we must interpret our results cautiously.

Value of the Electrocardiogram as a Predictor of Right Ventricular Dysfunction in Patients With Chronic Right Ventricular Volume Overload.

INTRODUCTION AND OBJECTIVES: Pulmonary regurgitation is a common complication in patients with repaired tetralogy of Fallot or congenital pulmonary stenosis. Electrocardiographic variables have been correlated with parameters used to evaluate right ventricular function. We aimed to analyze the diagnostic value of the width and fragmentation of the electrocardiogram in the identification of patients with right ventricular dysfunction and/or dilation. METHODS: We selected 107 consecutive patients diagnosed with severe pulmonary insufficiency after repair of pulmonary stenosis or tetralogy of Fallot. The tests included electrocardiography, echocardiography, and magnetic resonance. Each electrocardiogram was analyzed manually to measure QRS duration. We defined QRS fragmentation as the presence of low-voltage waves in the terminal portion of the QRS complex in at least 2 contiguous leads. RESULTS: We found a significant negative correlation between QRS width and right ventricular function, as well as a positive correlation with right ventricular volume. The receiver operating characteristic curve indicated a cut-off point for QRS width of 140ms, which showed good sensitivity for a diagnosis of right ventricular dilation (> 80%) and dysfunction (> 95%). In logistic regression models, a QRS duration > 140ms was found to be the only independent predictor of right ventricular dilation and dysfunction. CONCLUSIONS: Electrocardiography is a rapid, widely available, and reproducible tool. QRS width constitutes an independent predictor of the presence of right ventricular dilation and dysfunction. This study is the first to provide a cutoff value for QRS width to screen for right ventricle involvement.

Long term effects of cocaine on the heart assessed by cardiovascular magnetic resonance at 3T.

BACKGROUND: Cocaine is an addictive, sympathomimetic drug with potentially lethal effects. The prevalence and features of cocaine cardiotoxicity are not well known. We aimed to assess these effects using a comprehensive cardiovascular magnetic resonance (CMR) protocol in a large group of asymptomatic cocaine users. METHODS: Consecutive (n = 94, 81 males, 36.6 ±7 years), non-selected, cocaine abusers were recruited and had a medical history, examination, ECG, blood test and CMR. The CMR study included measurement of left and right ventricular (LV, RV) dimensions and ejection fraction (EF), sequences for detection of myocardial oedema and late gadolinium enhancement (LGE). Images were compared to a cohort of healthy controls. RESULTS: Years of regular cocaine use were 13.9 ± 9. When compared to the age-matched healthy cohort, the cocaine abusers had increased LV end-systolic volume, LV mass index and RV end-systolic volume, with decreased LVEF and RVEF. No subject had myocardial oedema, but 30% had myocardial LGE indicating myocardial damage. CONCLUSIONS: CMR detected cardiovascular disease in 71% of this cohort of consecutive asymptomatic cocaine abusers and mean duration of abuse was related to probability of LV systolic dysfunction.

[Arrhythmogenic cardiomyopathy. Patterns of ventricular involvement using cardiac magnetic resonance]. / Resonancia magnética cardiaca en miocardiopatía arritmogénica. Tipos de afección y patrones de realce tardío de gadolinio.

INTRODUCTION AND OBJECTIVES: Biventricular arrhythmogenic cardiomyopathy and left dominant arrhythmogenic cardiomyopathy forms had recently been included in the spectrum of arrhythmogenic cardiomyopathy. The aim of the study was to describe, using cardiovascular magnetic resonance, the patterns of ventricular involvement as well as late gadolinium enhancement in these conditions. METHODS: Medical databases and records from the cardiology units of 3 hospitals were reviewed to obtain data from patients with arrhythmogenic cardiomyopathy. RESULTS: Twenty-six consecutive patients were included (40 [16] years, 16 males). Right ventricle involvement was present in 19 patients (73%). Among them, 13 patients (50%) had volumes over the upper limit of normality, 11 (42%) patients had late gadolinium enhancement in right ventricle and 6 patients (23%) had just mild involvement with wall motion abnormalities or microaneurysms. Left ventricle involvement was present in 24 patients (92%), all of them with late gadolinium enhancement. In 15 patients (57%) left ventricular systolic dysfunction was observed, and dilatation in 3 patients (11%). Late gadolinium enhancement was more frequent in the inferior, lateral, and inferolateral walls (65%, 57%, and 61% of patients, respectively) while septum was seldom affected (26% of cases). The pattern of late gadolinium enhancement was mainly subepicardial (46% of patients) or transmural (19%), and was intramyocardial in only 12% of the cases. CONCLUSIONS: In this sample, left ventricle involvement is very common. The most frequent finding was left ventricular late gadolinium enhancement, while the least frequent was dilatation. The pattern of late gadolinium enhancement was more frequently subepicardial and located in the inferior and inferolateral walls.

[Left dominant arrhythmogenic cardiomyopathy caused by a novel nonsense mutation in desmoplakin]. / Miocardiopatía arritmogénica con afectación predominante del ventrículo izquierdo por una mutación nueva «sin sentido¼ en desmoplaquina.

Left dominant arrhythmogenic cardiomyopathy (LDAC) exhibits characteristic phenotypic and genetic features which were found in the five Spanish family members described in this study. Triggered by a cold, a young man presented with a ventricular tachycardia of left ventricular origin and left ventricular late gadolinium enhancement. His resting ECG showed low potentials, delayed ventricular depolarization (inferior and V4-V6 leads) and atrioventricular conduction disturbances. His endomyocardial biopsy revealed myocyte loss with interstitial fibrosis. Despite the initial diagnosis of myocarditis, familial screening was pivotal in confirming the diagnosis of LDAC. A novel nonsense mutation in the desmoplakin gene (Q1866X) and the truncated protein which it produces were observed in skin samples.

Cardiac magnetic resonance imaging at 1.5 T in patients with cardiac rhythm devices.

AIMS: Recent studies suggest that non-cardiac magnetic resonance imaging (MRI) scanning can be performed safely in selected cardiac rhythm device patients. However, little is known about the safety of performing specific cardiac MRI in this setting. We sought to determine the feasibility of cardiac MRI in patients with pacemakers (PMs) or implantable cardioverter-defibrillators (ICDs). METHODS AND RESULTS: Thirty-eight patients underwent a total of 39 (8 ICDs and 31 PM) cardiac MRI examinations at 1.5 T using usual protocols without specific absorption rate (SAR) restrictions. Nine PM-dependent patients were included. All devices were interrogated before and immediately after MRI. During the scan, pacing mode was programmed to asynchronous for PM-dependent patients whereas ICDs were programmed to a monitor-only mode. All devices were functioning appropriately after cardiac MRI. Comparison of device parameters obtained before and immediately after MRI revealed no significant changes in pacing threshold, lead impedance, battery status, or sensing signal amplitude. Neither clinical events nor patient complaints were reported. Significant imaging artefacts were present on 11 of 39 scans (28.2%). These artefacts were significantly more frequent in ICDs (8 of 8, 100%) vs. PMs (3 of 31, 9.7%) (P < 0.001). Diagnostic questions were answered in 92.3% of the cases, with just three pronounced artefacts preventing an adequate diagnosis in three ICD patients. CONCLUSIONS: Our results suggest that cardiac MRI may be performed safely in appropriately selected patients with close monitoring during the scan without limitation of peak SAR level using several precautionary measures. Image artefacts were more frequent in ICD patients.

Nuclear magnetic resonance imaging in patients with cardiac pacing devices.

Currently, nuclear magnetic resonance imaging is contraindicated in patients with a pacemaker or implantable cardioverter-defibrillator. This study was carried out because the potential risks in this situation need to be clearly defined. This prospective study evaluated clinical and electrical parameters before and after magnetic resonance imaging was performed in 33 patients (five with implantable cardioverter-defibrillators and 28 with pacemakers). In these patients, magnetic resonance imaging was considered clinically essential. There were no clinical complications. There was a temporary communication failure in two cases, sensing errors during imaging in two cases, and a safety signal was generated in one pacemaker at the maximum magnetic resonance frequency and output level. There were no technical restrictions on imaging nor were there any permanent changes in the performance of the cardiac pacing device.

[Reliability of cardiac magnetic resonance imaging indicators of myocardial viability for predicting the recovery of systolic function after a first acute myocardial infarction with a patent culprit artery]. / Fiabilidad de los índices de viabilidad miocárdica por resonancia magnética para predecir la mejoría de la función sistólica en pacientes con un primer infarto reciente y arteria abierta.

INTRODUCTION AND OBJECTIVE: To assess the reliability of early analysis of the most frequently used cardiac magnetic resonance (CMR)-derived indexes for predicting systolic function recovery and ventricular remodeling in patients after a first acute myocardial infarction with a patent culprit artery. PATIENTS AND METHOD: 17 patients were studied with an initial CMR protocol that included regional assessment of wall thickness and wall thickening, low-dose dobutamine response, first-pass gadolinium myocardial perfusion imaging and delayed enhancement. These results were compared with those obtained for segmental and global function in a second CMR study 6 months later. RESULTS: Of the 272 myocardial segments evaluated in the initial study, 73 showed severe systolic dysfunction. The findings were used to calculate sensitivity and specificity of each of the indexes mentioned above for predicting myocardial viability. The sensitivities and specificities for each index were wall thickness > or =5.5 mm, 100% and 12%; low-dose dobutamine response, 41% and 93%; normal myocardial perfusion, 78% and 68%; delayed enhancement, 81% and 95%. Multivariate analysis showed that delayed enhancement was the only independent predictor of contractility (r=-0.83, P=.0001), ventricular volumes (end-diastolic: r=0.61, P=.009, end-systolic: r=0.67, P=.003) and ejection fraction (r=-0.73, P=.001) at 6 months. CONCLUSIONS: Delayed enhancement seen in CMR is a reliable, quantifiable index for predicting recovery of systolic function and ventricular remodeling in patients after a first infarction with a patent culprit artery.

[Usefulness of magnetic resonance imaging in the assessment of endomyocardial disease]. / Utilidad de la resonancia magnética en el estudio de la enfermedad endomiocárdica.

Endomyocardial disease is a restrictive cardiomyopathy that includes Löffler endocarditis, which is characterized by hypereosinophilia, and endomyocardial fibrosis, which is not. Echocardiography enables cardiac function and anatomy to be assessed and the differential diagnosis of other causes of restrictive disease, but magnetic resonance imaging provides information about the tissue itself. Furthermore, paramagnetic contrast agents are useful in detecting myocardial abnormalities. We report three cases of endomyocardial disease and the typical findings of magnetic resonance imaging.